Pruritus is also called itch. Pruritus (like pain) is not a disease, but a symptom of a disease (condition, disorder) that causes the expression of pruritus. Thus, pruritus (like pain) is a warning signal, telling the patient that some underlying disorder is present. The terms “condition”, “disease”, and “disorder” are synonyms and are often called “underlying condition”, “underlying disease” or “underlying disorder” in connection with pain or pruritus.
Pruritus is an unpleasant sensation that elicits the desire to scratch. Acute pruritus is a frequent experience in most mammalian species and can usually be abolished by scratching at the area of the itching. Chronic pruritus can be debilitating and scratching provides no or very little relief; actually, scratching most often exacerbates the problem. As used herein, the terms “pruritus”, “pruritic”, “itch”, “itching” etc. refer to chronic pruritus.
Pruritus is experienced by many mammals, including humans. Pruritus in humans can be caused by various underlying diseases, such as for example dermatological disorders, neurological disorders, systemic disorders and by drugs with pruritic side effects. Pruritus in dogs is also common and usually caused by parasites, various allergens or underlying diseases. Canine pruritus is rarely successfully treated with antihistamines. Thus pruritic dogs almost exclusively suffer from non-histaminergic itch. Pruritus in cats is usually caused by parasites or allergens or other conditions. Cats react to itchiness in similar ways as dogs. Thus, both cats and dogs are scratching, licking and biting. However, contrary to dogs, up to 50 percent of cats with pruritus seem to have histamine-sensitive types of pruritus, while the remaining pruritic cats suffer from non-histaminergic forms of pruritus. Pruritus in horses is very common and is one of the most common reasons for horse owners to seek help from veterinarians. A horse with itchy skin will rub up against fences, stalls, trees, or other objects while attempting to scratch the itch. The horse may excessively bite or lick its skin to the point of causing bleeding or damage to the skin. The most common causes of allergic itching in horses are insect bites, food allergies including allergens in horse feed, and itching due to seasonal allergens. Pruritus in horses is seldom treated successfully with antihistamines, indicating that pruritus in horses usually is non-histaminergic pruritus.
The lack of success of antihistamines in treating pruritus suggests that treatments for non-histaminergic pruritus are needed across species.
Patients suffering from histamine-induced pruritus can be treated with inhibitors (inverse agonists) of histamine H-1 receptors, such as for example desloratadine or diphenhydramine, or by histamine H-2 receptor inhibitors, such as for example cimetidine and ranitidine, or—when they become commercially available—by histamine H-4 receptor inhibitors, such as for example JNJ 7777120. Such treatments, however, are ineffective in the treatment of non-histaminergic pruritus.
Human patients suffering from non-histaminergic pruritus usually try medications, such as corticosteroids, antiepileptic drugs, opioid receptor antagonists, antidepressants or local anesthetics to relive itch, however, such medications are relatively unsuccessful. In addition, the anti-epileptic drug gabapentin, which impedes signals transmitting pain and pruritus to the brain, may offer some relief for human patients who can withstand the severe adverse events caused by this drug.
What is needed are treatments for non-histaminergic pruritus that are both effective and free from debilitating side effects.